Chemonucleolysis with chymopapain has been suggested as an alternative to surgical removal of the nucleus pulposis for degenerative disc disease. Clinical observations following the use of this enzyme have suggested that the nucleus may have the ability to regenerate. 1) We hypothesize that enzymatic dissolution of the nucleus pulposis using chymopapain or other proteoglycanase enzymes produces a reversible dissolution of the nucleus; 2) Enzymes may be available for chemonucleolysis that are equally effective as chymopapain but have less side effects in the regeneration process. In order to test these hypotheses we propose: 1) To determine the early and delayed biochemical effects of chymopapain on the intervertebral disc in experimental animals. This study will consist of both short-term and long-term evaluation of the nature of the reconstituted annulus and nucleus in terms of its microscopic appearance and biochemical composition including collagen type, proteoglycans, and matrix proteins; 2) To test alternative enzymes such as clostripain, protease K and microprotease under similar experimental conditions to determine if these enzymes act similarly to chymopapain in experimental animals in vivo, and hence whether they might be considered as possible substitutes to chymopapain for chemical dissolution of the intervertebral disc. It is anticipated that the results from these studies will have important clinical implication in the treatment of common human diseases.